Tailorable optical properties of polymer nanodots for triple-mode fluorescence detection of nucleic acids.

We present a triple-mode nanosensor platform for nucleic acid detection utilizing fluorescence anisotropy and Förster resonance energy transfer (FRET) strategies. The self-assembled nanoprobes serve as mass amplifiers, nanoquenchers, or nanodonors, exhibiting high FRET efficiencies (64.4-86.5%) and demonstrating excellent detection capabilities in DNA and microRNA analysis.

Cardiologist-level interpretable knowledge-fused deep neural network for automatic arrhythmia diagnosis.

BACKGROUND: Long-term monitoring of Electrocardiogram (ECG) recordings is crucial to diagnose arrhythmias. Clinicians can find it challenging to diagnose arrhythmias, and this is a particular issue in more remote and underdeveloped areas. The development of digital ECG and AI methods could assist clinicians who need to diagnose arrhythmias outside of the hospital setting. METHODS: We constructed a large-scale Chinese ECG benchmark dataset using data from 272,753 patients collected from January 2017 to December 2021. The dataset contains ECG recordings from all common arrhythmias present in the Chinese population. Several experienced cardiologists from Shanghai First People's Hospital labeled the dataset. We then developed a deep learning-based multi-label interpretable diagnostic model from the ECG recordings. We utilized Accuracy, F1 score and AUC-ROC to compare the performance of our model with that of the cardiologists, as well as with six comparison models, using testing and hidden data sets. RESULTS: The results show that our approach achieves an F1 score of 83.51%, an average AUC ROC score of 0.977, and 93.74% mean accuracy for 6 common arrhythmias. Results from the hidden dataset demonstrate the performance of our approach exceeds that of cardiologists. Our approach also highlights the diagnostic process. CONCLUSIONS: Our diagnosis system has superior diagnostic performance over that of clinicians. It also has the potential to help clinicians rapidly identify abnormal regions on ECG recordings, thus improving efficiency and accuracy of clinical ECG diagnosis in China. This approach could therefore potentially improve the productivity of out-of-hospital ECG diagnosis and provides a promising prospect for telemedicine.

Arrhythmia, also known as an irregular heartbeat, is a common cardiovascular disease. Sometimes the presence of an arrhythmia can increase the risk of more serious heart conditions. Long-term monitoring of the heartbeat enables arrhythmia to be more easily diagnosed. To accurately detect arrhythmia, we developed a computational model that was able to detect six common types of arrhythmias from readings of the heart rate obtained using a device connected to a mobile phone. We showed that our model could diagnose these arrhythmias in over 270,000 people living in China. Our diagnostic system could enable arrhythmias to be diagnosed more easily outside of hospitals and therefore improve access to healthcare, particularly for those in remote settings.

Effective Bidirectional Mott-Schottky Catalysts Derived from Spent LiFePO4 Cathodes for Robust Lithium-Sulfur Batteries.

It is deemed as a tough yet profound project to comprehensively cope with a range of detrimental problems of lithium-sulfur batteries (LSBs), mainly pertaining to the shuttle effect of lithium polysulfides (LiPSs) and sluggish sulfur conversion. Herein, a Co2 P-Fe2 P@N-doped carbon (Co2 P-Fe2 P@NC) Mott-Schottky catalyst is introduced to enable bidirectionally stimulated sulfur conversion. This catalyst is prepared by simple carbothermal reduction of spent LiFePO4 cathode and LiCoO2 . The experimental and theoretical calculation results indicate that thanks to unique surface/interface properties derived from the Mott-Schottky effect, full anchoring of LiPSs, mediated Li2 S nucleation/dissolution, and bidirectionally expedited "solid⇌liquid⇌solid" kinetics can be harvested. Consequently, the S/Co2 P-Fe2 P@NC manifests high reversible capacity (1569.9 mAh g-1 ), superb rate response (808.9 mAh g-1 at 3C), and stable cycling (a low decay rate of 0.06% within 600 cycles at 3C). Moreover, desirable capacity (5.35 mAh cm-2 ) and cycle stability are still available under high sulfur loadings (4-5 mg cm-2 ) and lean electrolyte (8 µL mg-1 ) conditions. Furthermore, the as-proposed universal synthetic route can be extended to the preparation of other catalysts such as Mn2 P-Fe2 P@NC from spent LiFePO4 and MnO2 . This work unlocks the potential of carbothermal reduction phosphating to synthesize bidirectional catalysts for robust LSBs.

Huanglian Jiedu Wan intervened with "Shi-Re Shanghuo" syndrome through regulating immune balance mediated by biomarker succinate.

With increasing stress in daily life and work, subhealth conditions induced by "Shi-Re Shanghuo" syndrome was gradually universal. "Huanglian Jiedu Wan" (HLJDW) was the first new syndrome Chinese medicine approved for the treatment of "Shi-Re Shanghuo" with promising clinical efficacy. Preliminary small-sample clinical studies have identified some notable biomarkers (succinate, 4-hydroxynonenal, etc.). However, the correlation and underlying mechanism between these biomarkers of HLJDW intervention on "Shi-Re Shanghuo" syndrome remained ambiguous. Therefore, this study was designed as a randomized, double-blind, multicenter, placebo-controlled Phase II clinical trial, employing integrated analysis techniques such as non-targeted and targeted metabolomics, salivary microbiota, proteomics, parallel peaction monitoring, molecular docking and surface plasmon resonance (SPR). The results of the correlation analysis indicated that HLJDW could mediate the balance between inflammation and immunity through succinate produced via host and microbial source to intervene "Shi-Re Shanghuo" syndrome. Further through the HIF1α/MMP9 pathway, succinate regulated downstream arachidonic acid metabolism, particularly the lipid peroxidation product 4-hydroxynonenal. Finally, an animal model of recurrent oral ulcers induced by "Shi-Re Shang Huo" was established and HLJDW was used for intervention, key essential indicators (succinate, glutamine, 4-hydroxynonenal, arachidonic acid metabolism) essential in the potential pathway HIF1α/MMP9 discovered in clinical practice were validated. The results were found to be consistent with our clinical findings. Taken together, succinate was observed as an important signal that triggered immune responses, which might serve as a key regulatory metabolic switch or marker of "Shi-Re Shanghuo" syndrome treated with HLJDW.

[Study on biomarkers of acteoside in treating puromycin aminonucleoside nephropathy in young rats based on non-targeted urine metabolomics technology].

This study aims to reveal the endogenous metabolic characteristics of acteoside in the young rat model of purinomycin aminonucleoside nephropathy(PAN) by non-targeted urine metabolomics and decipher the potential mechanism of action. Biochemical indicators in the urine of rats from each group were determined by an automatic biochemical analyzer. The potential biomarkers and related core metabolic pathways were identified by ultra-high performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS) combined with principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). MetaboAnalyst 5.0 was used to establish the receiver operating characteristic(ROC) curve for evaluating the clinical diagnostic performance of core metabolites. The results showed that acteoside significantly decreased urinary protein-to-creatinine ratio in PAN young rats. A total of 17 differential metabolites were screened out by non-targeted urine metabolomics in PAN young rats and they were involved in phenylalanine metabolism and phenylalanine, tyrosine and tryptophan biosynthesis. Thirtten differential metabolites were screened by acteoside intervention in PAN young rats, and they were involved in phenylalanine metabolism and arginine and proline metabolism. Among them, leucylproline and acetophenone were the differential metabolites that were significantly recovered after acteoside treatment. These pathways suggest that acteoside treats PAN in young rats by regulating amino acid metabolism. The area under the curve of two core biomarkers, leucylproline and acetophenone, were both greater than 0.9. In summary, acteoside may restore amino acid metabolism by regulating endogenous differential metabolites in PAN young rats, which will help to clarify the mechanism of acteoside in treating chronic glomerulonephritis in children. The characteristic biomarkers screened out have a high diagnostic value for evaluating the treatment of chronic glomerulonephritis in children with acteoside.

[Component profile analysis of Sanhan Huashi Formula based on UHPLC-LTQ-Orbitrap-MS, GC-MS, and UHPLC-QQQ-MS/MS].

This study comprehensively analyzed the active components of Sanhan Huashi Formula using qualitative and quantitative mass spectrometry techniques, laying the foundation for understanding its pharmacological substance basis. UHPLC-LTQ-Orbitrap-MS and GC-MS technologies were used to analyze and identify the volatile and non-volatile components in Sanhan Huashi Formula. UHPLC-QQQ-MS/MS technology was used to simultaneously determine the content of 27 major active components in the formula. The results showed that 308 major chemical components were identified in Sanhan Huashi Formula, among which 60 compounds were identified by comparing with reference standards, mainly including alkaloids, flavonoids, coumarins, triterpenoid saponins, amino acids, and nucleosides. GC-MS technology preliminarily identified 52 volatile compounds, with γ-eudesmol and ß-eudesmol as the main components. The quantitative results demonstrated good linearity(r>0.99) for the 27 active components, indicating the stability, simplicity, and reliability of the established method. Among them, amygdalin, nodakenin, arecoline, ephedrine, and pseudoephedrine had relatively high content and were presumably the main pharmacologically active substances. In conclusion, this study systematically and comprehensively characterized the major chemical components and patterns in Sanhan Huashi Formula, providing a basis for understanding its pharmacological mechanisms and clinical applications.

Biotransformed bear bile powder ameliorates diet-induced nonalcoholic steatohepatitis in mice through modulating arginine biosynthesis via FXR/PXR-PI3K-AKT-NOS3 axis.

NASH is a highly prevalent metabolic syndrome that has no specific approved agents up to now. BBBP, which mainly contains bile acids, possess various pharmacological properties and some bile acids are available for NASH treatment. Herein, the therapeutic effects and underlying mechanisms of BBBP against NASH were systemically evaluated. In this study, mice received an HFHS diet over a 20-week period to induce NASH with or without BBBP intervention were used to evaluate the effect and underlying mechanisms of BBBP against NASH. Our results demonstrated that BBBP attenuated hepatic steatosis, reduced body weight gain and lipid concentrations, and improved sensitivity to insulin and tolerance to glucose in mice fed an HFHS diet. Metabolomics and transcriptomic analysis revealed that BBBP suppressed the arginine biosynthesis by up-regulating NOS3 expression and the PI3K-Akt signaling pathway was also regulated by BBBP, as indicated by 55 DEGs. Bioinformatic analysis predicted the regulatory effect of the FXR/PXR-PI3K-AKT-NOS3 axis on arginine biosynthesis-related metabolites. These results were further confirmed by the significantly increased mRNA and protein levels of NOS3, PI3K (Pik3r2), and AKT1. And the increased levels of arginine biosynthesis related-metabolites, such as urea, aspartic acid, glutamic acid, citrulline, arginine, and ornithine, were confirmed accurately based on targeted metabolomics analysis. Together, our study uncoded the complicated mechanisms of anti-NASH activities of BBBP, and provided critical evidence inspiring the discovery of innovative therapies based on BBBP in the treatment of NASH.

Association Between Mean Platelet Volume and Benign Prostatic Hyperplasia: A Population Study from the TCLSIH Cohort Study.

Purpose: This study aimed to prospectively investigate the association between mean platelet volume (MPV) levels and risk of benign prostatic hyperplasia (BPH) in a general Chinese adult male population, and assessed this association in metabolic syndrome (MetS) patients. Patients and methods: This study included a total of 14,923 male participants free from BPH at baseline. MPV was measured by the method of laser-based flow cytometric impedance according to the complete blood sample. BPH was defined as total prostate volume (TPV) ≥ 30 mL, TPV was determined by transabdominal ultrasonography. Multivariable Cox proportional hazards models were fitted to calculate hazards ratios (HRs) and corresponding 95% confidence intervals (CIs) for BPH risk with NLR levels. Results: During a median follow-up of 2.7 years, 4848 BPH cases were documented in total male participants, and 1787 BPH cases were documented in MetS participants. After adjusting for age, body mass index, smoking, alcohol and personal and family history of disease, the multivariable-adjusted HRs of BPH were 1.00 (reference), 1.03 (95% CIs 0.96, 1.11), 1.00 (95% CIs 0.92, 1.08) and 0.98 (95% CIs 0.90, 1.06), respectively, for participants with MPV in the 1st, 2nd, 3rd and 4th quartiles (P for trend = 0.47). In MetS patients, the multivariable-adjusted HRs of BPH were 1.00 (reference), 1.03 (95% CIs 0.90, 1.16), 0.99 (95% CIs 0.87, 1.14) and 1.01 (95% CIs 0.89, 1.15) (P for trend= 0.98), respectively. Conclusion: A non-significant association was observed between MPV levels and risk of BPH, and no association in this association in MetS patients. Our findings support the notion that MPV levels may not be a target for BPH prevention and intervention.

Comparison of performance and clinical utility of different methods for detecting anti-PLA2R antibody.

OBJECTIVES: This study aimed to compare the performance of enzyme-linked immunosorbent assay (ELISA) and magnetic particle chemiluminescence immunoassay (MP-CLIA) for detecting anti-phospholipase A2 receptor (PLA2R) antibody and their clinical significance in idiopathic membranous nephropathy (IMN) patients. METHODS: Serum samples from 448 patients with different types of nephropathy, including 222 with IMN, were tested using both methods. Sensitivity, specificity, and prognostic significance of PLA2R antibody levels were evaluated. RESULTS: Similar sensitivity and specificity of ELISA and MP-CLIA in identifying IMN patients was found. However, MP-CLIA performed better than ELISA in predicting the prognosis of IMN patients. Adjusting the cutoff value reduced the false-negative rate in both methods. Logistic regression analysis identified six variables, including MP-CLIA-PLA2R levels, eGFR, lymphocyte count, B lymphocyte count, NK cell count, and complement 4, as predictors of renal function outcomes in IMN patients. CONCLUSIONS: Both ELISA and MP-CLIA are reliable methods for detecting anti-PLA2R antibodies in IMN patients. However, MP-CLIA is more accurate in predicting the prognosis of IMN. Combining MP-CLIA-PLA2R with other variables can help predict renal function outcomes in IMN patients. Our study emphasizes the importance of considering both analytical performance and clinical utility when selecting a PLA2R antibody assay kit.

Global cardiovascular diseases burden attributable to high sodium intake from 1990 to 2019.

Sodium intake shows a positive correlation with blood pressure, resulting in an increased risk for cardiovascular diseases (CVD). Salt reduction is a key step toward the WHO's goal of 25% reduction in mortality from non-communicable diseases (NCDs) by 2025. This study aims to assess the current condition and temporal changes of the global CVD burden due to high sodium intake (HSI). We extracted data from the Global Burden of Disease (GBD) study 2019. The numbers and age-standardized rates of mortality and disability-adjusted life-years (DALYs), stratified by location, sex, and socio-demographic Index (SDI), were used to assess the high sodium intake attributable CVD burden from 1990 to 2019. The relationship between the DALYs rates and related factors was evaluated by stepwise multiple linear regression analysis. Globally, in 2019, the deaths and DALYs of HSI-related CVD were 1.72 million and 40.54 million, respectively, increasing by 41.08% and 33.06% from 1990. Meanwhile, the corresponding mortality and DALYs rates dropped by 35.1% and 35.2%, respectively. The high-middle and middle SDI quintiles bore almost two-thirds of CVD burden caused by HSI. And the leading cause of HSI attributable CVD burden was ischemic heart disease. Universal health coverage (UHC) was associated with the DALYs rates after adjustment. From 1990 to 2019, the global CVD burden attributable to HSI has declined with spatiotemporal and sexual heterogeneity. However, it remains a major public health challenge because of the increasing absolute numbers. Improving UHC serves as an effective strategy to reduce the HSI-related CVD burden.

Profiling neurotransmitter-evoked glial responses by RNA-sequencing analysis.

Fundamental properties of neurons and glia are distinctively different. Neurons are excitable cells that transmit information, whereas glia have long been considered as passive bystanders. Recently, the concept of tripartite synapse is proposed that glia are structurally and functionally incorporated into the synapse, the basic unit of information processing in the brains. It has then become intriguing how glia actively communicate with the presynaptic and postsynaptic compartments to influence the signal transmission. Here we present a thorough analysis at the transcriptional level on how glia respond to different types of neurotransmitters. Adult fly glia were purified from brains incubated with different types of neurotransmitters ex vivo. Subsequent RNA-sequencing analyses reveal distinct and overlapping patterns for these transcriptomes. Whereas Acetylcholine (ACh) and Glutamate (Glu) more vigorously activate glial gene expression, GABA retains its inhibitory effect. All neurotransmitters fail to trigger a significant change in the expression of their synthesis enzymes, yet Glu triggers increased expression of neurotransmitter receptors including its own and nAChRs. Expressions of transporters for GABA and Glutamate are under diverse controls from DA, GABA, and Glu, suggesting that the evoked intracellular pathways by these neurotransmitters are interconnected. Furthermore, changes in the expression of genes involved in calcium signaling also functionally predict the change in the glial activity. Finally, neurotransmitters also trigger a general metabolic suppression in glia except the DA, which upregulates a number of genes involved in transporting nutrients and amino acids. Our findings fundamentally dissect the transcriptional change in glia facing neuronal challenges; these results provide insights on how glia and neurons crosstalk in a synaptic context and underlie the mechanism of brain function and behavior.

Cyclin-G-associated kinase GAK/dAux regulates autophagy initiation via ULK1/Atg1 in glia.

Autophagy is a major means for the elimination of protein inclusions in neurons in neurodegenerative diseases such as Parkinson's disease (PD). Yet, the mechanism of autophagy in the other brain cell type, glia, is less well characterized and remains largely unknown. Here, we present evidence that the PD risk factor, Cyclin-G-associated kinase (GAK)/Drosophila homolog Auxilin (dAux), is a component in glial autophagy. The lack of GAK/dAux increases the autophagosome number and size in adult fly glia and mouse microglia, and generally up-regulates levels of components in the initiation and PI3K class III complexes. GAK/dAux interacts with the master initiation regulator UNC-51like autophagy activating kinase 1/Atg1 via its uncoating domain and regulates the trafficking of Atg1 and Atg9 to autophagosomes, hence controlling the onset of glial autophagy. On the other hand, lack of GAK/dAux impairs the autophagic flux and blocks substrate degradation, suggesting that GAK/dAux might play additional roles. Importantly, dAux contributes to PD-like symptoms including dopaminergic neurodegeneration and locomotor function in flies. Our findings identify an autophagy factor in glia; considering the pivotal role of glia under pathological conditions, targeting glial autophagy is potentially a therapeutic strategy for PD.

Self-assembled nanoparticle with E protein domain III of DTMUV based on ferritin as carrier can induce a more comprehensive immune response and against DTMUV challenge in duck.

Duck Tembusu virus (DTMUV) causes severe reduction in egg production and neurological symptoms in ducklings. Vaccination is the primary measure used to prevent DTMUV infections. In this study, self-assembled nanoparticles with the E protein domain III of DTMUV, using ferritin as a carrier (EDⅢ-RFNp), were prepared using a prokaryotic expression system. Ducks were intramuscularly vaccinated with EDⅢ-RFNp, EDⅢ protein, an inactivated vaccine HB strain (InV-HB), and PBS. At 0, 4, and 6 weeks post-primary vaccination, the EDIII protein-specific antibody titre, IL-4, and IFN-γ concentrations in serum were determined by ELISA, and neutralising antibodies titres in sera were determined by virus neutralising assay. Peripheral blood lymphocytes proliferation was determined by CCK-8 kit. Following challenge with the virulent DTMUV strain, the clinical signals and survival rate of the vaccinated ducks were recorded, and DTMUV RNA levels in the blood and tissues of the surviving ducks were determined by real-time quantitative RT-PCR. The near-spherical EDⅢ-RFNp nanoparticles with 13.29 ± 1.43 nm diameter were observed by transmission electron microscope. At 4 and 6 weeks post-primary vaccination, special and Virus neutralisation (VN) antibodies, lymphocyte proliferation (stimulator index, SI), and concentrations of IL-4 and IFN-γ in the EDⅢ-RFNp group were significantly higher than in the EDⅢ and PBS groups. In the DTMUV virulent strain challenge test, the EDⅢ-RFNp-vaccinated ducks showed milder clinical signs and higher survival rates than EDⅢ- and PBS-vaccinated ducks. The DTMUV RNA levels in the blood and tissues of EDⅢ-RFNp-vaccinated ducks were significantly lower than those in EDⅢ- and PBS-vaccinated ducks. Additionally, the EDⅢ protein-special and VN antibodies, SI value, and concentration of IL-4 and IFN-γ in the InV-HB group was significantly higher than that of the PBS group at 4 and 6 weeks post-primary vaccination. InV-HB provided more efficient protection than PBS based on a higher survival rate, milder signals, and lower levels of the DTMUV virus in the blood and tissues. These results indicated that EDⅢ-RFNp effectively protected ducks against DTMUV challenge and could be a vaccine candidate to prevent DTMUV infection.

The economic value of personal protective equipment for healthcare workers.

In this paper, we examine the cost effectiveness of investment in personal protective equipment (PPE) for protecting health care workers (HCWs) against two infectious diseases: Ebola virus and methicillin-resistant Staphylococcus aureus (MRSA). This builds on similar work published for COVID-19 in 2020. We developed two separate decision-analytic models using a payer perspective to compare the costs and effects of multiple PPE use scenarios for protection of HCW against Ebola and MRSA. Bayesian multivariate sensitivity analyses were used to consider the uncertainty surrounding all key parameters for both diseases. We estimate the cost to provide adequate PPE for a HCW encounter with an Ebola patient is $13.04, which is associated with a 97% risk reduction in infections. The mean incremental cost-effectiveness ratio (ICER) is $3.98 per disability-adjusted life year (DALY) averted. Because of lowered infection and disability rates, this investment is estimated to save $132.27 in averted health systems costs, a financial ROI of 1,014%. For MRSA, the cost of adequate PPE for one HCW encounter is $0.88, which is associated with a 53% risk reduction in infections. The mean ICER is $362.14 per DALY averted. This investment is estimated to save $20.18 in averted health systems costs, a financial ROI of 2,294%. In terms of total health savings per death averted, investing in adequate PPE is the dominant strategy for Ebola and MRSA, suggesting that it is both more costly and less clinically optimal to not fully invest in PPE for these diseases. There are many compelling reasons to invest in PPE to protect HCWs. This analysis examines the economic case, building on previous evidence that protecting HCWs with PPE is cost-effective for COVD-19. Ebola and MRSA scenarios were selected to allow assessment of both endemic and epidemic infectious diseases. While PPE is cost-effective for both conditions, compared to our analysis for COVID-19, PPE is relatively more cost-effective for Ebola and relatively less so for MRSA. Further research is needed to assess shortfalls in the PPE supply chain identified during the COVID-19 pandemic to ensure an efficient and resilient supply in the face of future pandemics.

[Clinical application value of Huanglian Jiedu Pills in improving syndrome of excess heat and fire toxin based on phase â ¡ clinical trial study on plasma ATP, 4-HNE, and ACTH levels].

A randomized, double-blind, placebo-controlled, multi-center phase Ⅱ clinical trial design was used in this study to recruit subjects who were in line with the syndrome of excess heat and fire toxin, and were diagnosed as recurrent oral ulcers, gingivitis, and acute pharyngitis. A total of 240 cases were included and randomly divided into a placebo group and a Huanglian Jiedu Pills group. The clinical efficacy of Huanglian Jiedu Pills in treating the syndrome of excess heat and fire toxin was evaluated by using the traditional Chinese medicine(TCM) syndrome scale. Enzyme-linked immunosorbent assay(ELISA) was used to determine and evaluate the levels of adenosine triphosphate(ATP), 4-hydroxynonenal(4-HNE), and adrenocorticotropic hormone(ACTH) in plasma of the two groups before and after administration and to predict their application value as clinical biomarkers. The results showed that the disappearance rate of main symptoms in the Huanglian Jiedu Pills group was 69.17%, and that in the placebo group was 50.83%. The comparison between the Huanglian Jiedu Pills group and the placebo group showed that 4-HNE before and after administration was statistically significant(P<0.05). The content of 4-HNE in the Huanglian Jiedu Pills group decreased significantly after administration(P<0.05), but that in the placebo group had no statistical significance and showed an upward trend. After administration, the content of ATP in both Huanglian Jiedu Pills group and placebo group decreased significantly(P<0.05), indicating that the energy metabolism disorder was significantly improved after administration of Huanglian Jiedu Pills and the body's self-healing ability also alleviated the increase in ATP level caused by the syndrome of excess heat and fire toxin to a certain extent. ACTH in both Huanglian Jiedu Pills group and placebo group decreased significantly after administration(P<0.05). It is concluded that Huanglian Jiedu Pills has a significant clinical effect, and can significantly improve the abnormal levels of ATP and 4-HNE in plasma caused by the syndrome of excess heat and fire toxin, which are speculated to be the effective clinical biomarkers for Huanglian Jiedu Pills to treat the syndrome of excess heat and fire toxin.

A validated survey to measure Chinese hospital management practices.

Surveys are widely used to assess hospital management with the aim of understanding differences in management practices. However, survey measures with prior notice can make hospitals change their routine practices and are unable to reflect the actual hospital management level. The World Management Survey (WMS) methodology has been developed to ameliorate these issues. It uses a double-blinded method and open-ended question design. The Chinese Hospital Management Survey (CHMS) project is the first to adapt the WMS methodology in China, which it uses to measure hospital management level in 510 hospitals. This paper provides an instrument to better measure actual management practices, which makes it possible to compare the management level of hospitals in China and other countries.

The grading quality markers identification of Panax notoginseng under the guidance of traditional experience using untargeted metabolomics and anti-myocardial ischemia evaluation of zebrafish.

BACKGROUND: Panax notoginseng (PN) was an edible Chinese herbal medicine. PN's current quality control standard cannot precisely match the traditional grading experience. PURPOSE: In this study, under the guidance of the traditional grading experience, the combined metabolomics and biological effect evaluation were used to reveal the distinct chemical quality of PN. METHODS: The quality of PN was evaluated by traditional experience and characterized by the electronic tongue. A zebrafish myocardial ischemia model was developed to verify the grading experience. The untargeted metabolomics method was used to identify and validate the grading markers of PN. RESULTS: The taste was the critical indicator for classifying the quality. Based on the experience sensory scores (ranged from 47.0 to 87.8), PNs could be divided into two grades. The experience scores were significantly associated with umami and richness of the electronic tongue(p<0.01). Besides, superior PN showed substantially stronger anti-myocardial ischemia activity(p<0.001). Thirty-nine differential components were found using UHPLC-LTQ-Orbitrap MS, of which 22 were identified. A new kind of grading quality markers alkynols in PN-associated efficacy was identified, which revealed stronger anti-myocardial ischemia activities than saponin. CONCLUSION: This study evaluated PN through untargeted metabolomics and anti-myocardial ischemia evaluation of zebrafish and proposed the critical role of alkynols in PN's quality classification.

Studies on the metabolism and mechanism of acteoside in treating chronic glomerulonephritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Acteoside (ACT) is the main ingredient derived from the leaves of Rehmannia glutinosa (Dihuangye). Dihuangye has the function of clearing heat, replenishing qi and activating blood, nourishing yin and tonifying kidney in traditional Chinese medicine. Recent studies have demonstrated that Dihuangye can be used to treat nephritis and ACT is a promising antinephritic agent. AIM OF THE STUDY: To clarify the metabolites of ACT in biological samples and investigate the renoprotective effect and mechanism of ACT in rats with chronic glomerulonephritis (CGN). MATERIALS AND METHODS: In this study, the biotransformation of ACT in rat biological samples was clarified by quadrupole time-of-flight tandem mass spectrometry. The metabolites were validated by urine samples in nephropathy model rats. The effect of ACT and its metabolites was evaluated by glomerular podocyte injury due to high glucose. Based on an analysis of the ingredients in vivo, the potential therapeutic targets in the treatment of CGN were investigated by using network pharmacological analysis and molecular docking. Then, the renoprotective effect and mechanism of ACT were determined in rats in a passive Heymann nephritis (PHN) model. RESULTS: A total of 49 metabolites of ACT were detected and identified. Meanwhile, 21 metabolites were detected in nephropathy model rats. ACT was absorbed rapidly and transferred from the kidney, and the metabolites were eliminated via urine. The whole process lasted approximately 8 h. ACT had a significant protective effect on glomerular podocytes damaged by high glucose and 3,4-dihydroxyphenylacetic acid might be the main metabolite of ACT underlying its functions in vivo. The network pharmacology and molecular docking results showed 84 ACT-CGN targets, among which MAPK1, HRAS, AKT1, EGFR, and others were a highly correlated. In the PHN rat model, ACT significantly reduced the 24-h urine protein and serum creatinine concentrations, suppressed the leukocyte CD18 expression levels, decreased the serum tumor necrosis factor α (TNF-α) levels and tended to reduce serum interleukin 6 (IL-6) levels. ACT significantly reduced the platelet aggregation rate and inhibited the proliferative activity of splenic lymphocytes in response to the mitogen concanavalin A. Meanwhile, ACT inhibited transforming growth factor-ß and fibronectin expression in renal tissues and dose-dependently inhibited TNF-α and IL-6 production in RAW264.7 mouse macrophages at doses ranging from 1.8 to 1330 µg/mL. CONCLUSIONS: ACT had therapeutic effects on PHN rats, and its mechanism might be related to the inhibition of intercellular or intercellular-matrix adhesion, suppression of inflammatory response, regulation of immune function, improvement of tissue hemodynamics and hemorheology, and relief of fibrotic lesions.

Renal insufficiency predicts worse prognosis in newly diagnosed IgD multiple myeloma patients.

Objective: IgD multiple myeloma (MM) is a rare type of MM, accounting for about 1%-2% of all MMs. IgD MM always causes kidney damage and even leads to renal failure, which is the most common complication. This study aimed to explore the risk factors of renal damage and prognosis of IgD MM patients. Design: From March 2018 to November 2021, 85 patients with IgD MM diagnosed for the first time at the First Affiliated Hospital of Zhengzhou University were included in this study. We collected information on clinical features and laboratory examinations. Patients were divided into the renal impairment (RI) (47/85) and non-renal impairment (no-RI) (38/85) groups. Binary logistic regression was used to explore risk factors of renal damage. The Chi-square test was used to analyze the difference in chemotherapy effect between the two groups. We also analyzed whether early dialysis was beneficial to acute renal failure (RF) in IgD MM patients. Finally, Kaplan-Meier was used to compare the survival of the two groups. Results: In IgD MM, 55.3% of patients had renal damage as a complication, of which up to 59.6% presented with acute renal failure as the first manifestation. Serum ß2-microglobulin (ß2-MG) was an independent risk factor for renal damage in IgD MM (p = 0.002), but cytogenetic analysis suggested that it had no effect on patients' renal damage. There was also no significant difference in the effect of chemotherapy between the two groups (p = 0.255). In patients with acute renal failure, there was no significant difference between dialysis and no dialysis groups in the proportion of patients with improved renal function after treatment. The median overall survival (OS) of the RI group was significantly shorter than that of the no-RI group (p = 0.042). In the RI group, the median OS was 29 months, and in the no-RI group, the median OS was > 40 months. Conclusion: Elevated serum ß2-MG is an independent risk factor for renal damage. Compared with the no-RI group, patients in the RI group had poorer prognosis and shorter median OS. For patients with acute renal failure as the first manifestation, the treatment of primary disease is more meaningful than dialysis.

The safety and feasibility of laparoscopic right posterior sectionectomy vs. open approach: A systematic review and meta-analysis.

Background: Laparoscopic right posterior sectionectomy (LRPS) is one of the most technically challenging and potentially hazardous procedures in laparoscopic liver resection. Although some available literature works demonstrated the safety and feasibility of LRPS, these data are limited to reports from a single institution and a small sample size without support from evidence-based medicine. So, we performed a meta-analysis to assess further the safety and feasibility of LRPS by comparing it with open right posterior sectionectomy (ORPS). Methods: MEDLINE, Embase, and Cochrane Library were systematically searched for eligible studies comparing LRPS and open approaches. Random and fixed-effects models were used to calculate outcome measures. Results: Four studies involving a total of 541 patients were identified for inclusion: 250 in the LRPS group and 291 in the ORPS group. The postoperative complication and margin were not statistically different between the two groups (OR: 0.49, 95% CI: 0.18 to 1.35, P = 0.17) (MD: 0.05, 95% CI: -0.47 to 0.57, P = 0.86), respectively. LRPS had a significantly longer operative time and shorter hospital stay (MD: 140.32, 95% CI: 16.73 to 263.91, P = 0.03) (MD: -1.64, 95% CI: -2.56 to -0.72, P = 0.0005) respectively. Conclusion: Data from currently available literature suggest that LRPS performed by an experienced surgeon is a safe and feasible procedure in selected patients and is associated with a reduction in the hospital stay.